(A) Wall-eyed stereo view of CDP ribose and phosphate interactions with protein. CDP is shown as sticks with carbons in yellow. Protein side chain carbons are colored light purple and loop 2 residue, Arg298, carbons are colored tan. A putative water molecule is shown as a red sphere. Hydrogen-bonding interactions, shown with black dashed lines, include: O3' of ribose to Glu441, the proposed general base (van der Donk et al., 1996; Persson et al., 1997), and O2' to backbone carbonyl of Ser224. Cys225 is the proposed proton donor for the 2'-OH that is lost as H2O. Cys225 is 3.4–3.6 Å from the O2'. The distance between the sulfur atom of Cys439, where the thiyl radical is formed, and C3' of the ribose, where a hydrogen atom is abstracted to initiate catalysis, is 3.5–3.7 Å. (B) Wall-eyed stereo view of omit electron density for CDP structure shown in A. Orientation is tilted and rotated slightly to show the water density. A water molecule is present in this position in some substrate-bound RNR structures and not others, the significance of which is not clear. Arg298 is not shown for simplicity.